The spatial extent of retinal and choroidal damage will be probed with noninvasive, quantitative mapping of visual function and structure. We study the distinction between aging changes and disease processes, particularly for age-related macular degeneration (AMD). The goal is to determine why patients lose vision and then identify factors that are amenable to treatment to save vision. The long-term goals address 3 thrusts of the NEI National Plan for Eye and Vision Research: 1) develop and apply noninvasive technologies to better understand retinal function and changes in disease states; 2) improve early diagnosis of AMD; and 3) explore the pathophysiological heterogeneity of AMD to hasten development of the tools needed for improved diagnosis, prevention, and therapy. This project is one of the few that includes measurements of the visual cycle in living humans, including patients. We study patients with AMD and their family members, older control subjects, and young subjects, both as controls for family members of patients and to seek the very early changes in eye disease. [unreadable] [unreadable] We will use advanced imaging methods that are unique, rapid, and resistant to stray light. We probe both inner and outer retinal changes, to understand the environment of the photoreceptors. This includes the retinal pigment epithelium and retinal vascular changes. To investigate photoreceptor function, we will continue to develop novel methods to measure that photopigment within cones and rods in patients or regions of the retina not previously amenable to study. To our existing methods, we are adding new polarimetry techniques, including a multi-wavelength, scanning laser polarimeter. One unusual aspect is the use of multiply scattered light to provide information about pathology in and beneath the retina, otherwise obscured by the reflective retinal surface. Many of our methods use near infrared light, which improves patient comfort and provides views of the retina through moderate lens changes and fluid in the retina. [unreadable] [unreadable]